Project Summary/Abstract Viscoelastic properties of the human brain measured in vivo with magnetic resonance elastography (MRE) have shown great promise in diagnosing and staging neurological conditions. The objective of this work is to extend MRE methods for reliably mapping the mechanical properties of white matter (WM) tracts in the brain. Typical brain MRE methods have had minimal success in studying WM due to measurement inaccuracies and uncertainty caused by underlying assumptions in the MRE model. Specifically, MRE assumes tissue is mechanically isotropic ? i.e. properties are the same in each direction ? which is violated in WM that is mechanically anisotropic due to its well-ordered axonal fiber structure. To address this challenge, we propose to develop an anisotropic MRE (aMRE) approach that fuses three technological innovations to overcome the challenges limiting previous methods. In particular, we seek to use a simple but accurate model of fiber- reinforced tissue behavior; a robust inversion algorithm that models the heterogeneous nature of brain tissue; and a high-resolution imaging technique to capture displacement fields rich with diverse wave propagation. These elements represent the state-of-the-art in brain MRE and have been developed in the labs of the multiple PIs, and their integration in this research project will serve to significantly advance the field through a new methodology. This project encompasses three aims: (1) development of aMRE through the nonlinear inversion (NLI) algorithm with nearly-incompressible, transversely-isotropic (NITI) material model combined with a high-resolution, multi-excitation imaging scheme; (2) rigorous validation of the aMRE measurements through simulations, anisotropic phantoms, mini-pig brains in vivo and ex vivo; and (3) measurement of human brain WM mechanical properties in vivo. At the end of the project we will have developed and validated the novel aMRE technique for accurate and robust measures of WM mechanical properties of the human brain. We will have positioned aMRE to be used in the future study of neurological conditions that include WM damage or degeneration, such as multiple sclerosis and traumatic brain injury, through the sensitive assessment of microstructural health via mechanical properties.